This study tests an investigational cancer vaccine called ITI-5000 in people who have completed standard treatment for early-stage triple-negative breast cancer (TNBC).
ITI-5000 is a self-amplifying RNA (saRNA) vaccine that instructs the immune system to recognize and attack cancer cells expressing two proteins found on TNBC cells-HERV-K and CT83-fused with a molecule called LAMP-1 that helps the immune system respond more strongly. The vaccine is delivered inside lipid nanoparticles (LNPs), similar to other approved mRNA vaccines.
The study has two parts:
* Part A: Participants receive ITI-5000 alone at one of two dose levels (1 µg or 10 µg), given as an injection into the upper arm muscle every 28 days for 3 doses total. The goal is to find the safest dose. * Part B: Participants receive ITI-5000 at the best dose identified in Part A, combined with the following approved immunotherapy drugs pembrolizumab (Keytruda) and either olaparib or capecitabine.
Applicable to Part A only. Participants must have completed adjuvant pembrolizumab if they were receiving it before enrolling in the study.
Applicable to Cohort 3A and Part B only. Participant must have received neoadjuvant chemotherapy with pembrolizumab, then undergone definitive surgery. At the time of surgery, participant must not have achieved pCR.
Applicable to Part B only. Participant is currently receiving or is planned to receive standard of care adjuvant therapy, including pembrolizumab in combination with capecitabine or olaparib in accordance with the FDA-approved label, with ≥3 cycles remaining if receiving 200mg Q3W or ≥2 cycles remaining if receiving 400 mg Q6W at the time of first ITI-5000 dose.
Adults aged 18 years or over.
Applicable to Part B only. Participant discontinued prior treatment with an ICI due to irAEs.
Participant underwent major surgery within 4 weeks before the planned day of vaccination #1 or received any other investigational drug or device within 4 weeks or 5 half-lives of that agent (whichever is shorter) before the planned day of Vaccination #1.
Participant has toxicities due to prior immunotherapy. For the participant to be eligible, these toxicities must either have returned to ≤ Grade 1 or baseline or been deemed irreversible and in the opinion of the investigator not worsened by immunotherapy (e.g., ICI-endocrinopathies). Participants with any cardiac toxicities (regardless of the grade, etc.) will be excluded.
Participant has toxicities due to prior chemotherapy that have not been resolved or considered stable and clinically manageable (e.g., neuropathies). Participants with any cardiac toxicities will be excluded.
Parallel
ITI-5000 mRNA Vaccine
Biological/VaccineParticipants receive ITI-5000. Cohort 1 will receive 1 ug of vaccine
Pembrolizumab
DrugParticipants will receive ITI-5000 as an intramuscular injection every 21 days for 3 doses. Participants will also receive pembrolizumab as per the FDA-approved package insert.
ITI-5000 mRNA Vaccine
Biological/VaccineParticipants receive ITI-5000. Cohort 2 will receive 10 ug of vaccine
Olaparib
DrugParticipants will receive Olaparib in combination with Pembrolizumab and ITI-5000
Capecitabine
DrugParticipants will receive Capecitabine in combination with Pembrolizumab and ITI-5000
ITI-5000 MTD (Maximum Tolerated Dose)
Biological/VaccineParticipants receive ITI-5000 Maximum Tolerated Dose (MTD)
Incidence of Dose-Limiting Toxicities as Assessed by CTCAE v5.0
Incidence and severity of TEAEs, SAEs, treatment-related TEAEs, AESIs, and clinically significant abnormalities in laboratory parameters, vital signs, and ECGs
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